Mesenchymal stromal cells (MSCs) are derived from rare
mesenchymal stem cells. MSCs are present in every vascularised organ in the
body since they form part of the endothelium. For use in laboratory experiments
or clinical trials, MSCs need to be ex vivo expanded. This is readily achieved
by their adherence to plastic. We compared human bone marrow-derived MSCs with
human term placenta-derived MSCs and found them very similar in terms of cell
surface phenotype, mesodermal lineage differentiation ability and capacity to
suppress T cell alloreactivity in a mixed lymphocyte reaction in vitro. MSCs
exert their therapeutic benefit in at least four different ways:
differentiation into osteoblasts which produce osteoid material to heal
non-union bone fractures; paracrine secretion of immune modulatory proteins to
minimise exuberant inflammation in infarcted myocardium; transfer of MSC
mitochondria to acutely injured pulmonary cells; and apoptosis of T cells in
autoimmune disease. We have initiated two clinical trials using
placenta-derived MSCs. The first is in patients with idiopathic pulmonary
fibrosis. The first cohort of 4 patients have been infused intravenously with 1
x 106 MSCs/kg. No serious adverse events have occurred related to
the MSCs. Early results are encouraging and permission has been given by the
Data Safety Monitoring Committee to proceed to the next dose-level cohort. The
second trial is in patients with treatment-refractory Achilles tendinopathy.
The first cohort of 3 patients have been injected with MSCs intratendinously
with 1 x 106 MSCs. Again, no
serious adverse events have occurred related to the MSCs, and early results are
also encouraging. Permission has been given by the Data Safety Monitoring
Committee to proceed to the next dose-level cohort. We plan to expand our
clinical trial program to a wider range of disease settings. MSCs appear to
represent a useful first building block in the regenerative medicine
revolution.